Serum levels of fibroblast growth factor 21 are elevated in both rodents and humans in response to acute fasting

Abstract

Fibroblast growth factor 21 (FGF21) is a liver-secreted metabolic hormone with multiple beneficial effects on glucose and lipid metabolism. As its mRNA expression is induced by fasting, FGF21 has been proposed as a key regulator in coordinating carbohydrate and fatty acid metabolism during the progression from fasting to starvation. However, due to the lack of a reliable commercial assay for FGF21, changes in its circulating levels in response to fasting and refeeding remain poorly characterized. Data reported from animal and human studies so far are rather scarce and inconsistent. Here we have developed highly sensitive chemiluminescence immunoassays (CLIA) for both mouse and human FGF21. Using these assays, we found that serum FGF21 concentration in both mice and humans is markedly increased in response to overnight fasting. The serum level of FGF21 in C57 mice is elevated by 4.6 fold after fasting for 10 hours, and prolonged fasting for 48 hours causes a further elevation of serum FGF21 (6-fold higher compared to the fed state). Refeeding rapidly inhibits the secretion of FGF21. At one and a half hours after refeeding, the serum level of FGF21 in mice is decreased by more than 75%. In high fat-induced obese mice, the circulating levels of FGF21 in fed state are 6-fold higher than those in lean mice. However, the magnitude of FGF21 increase induced by overnight fasting in those dietary obese mice is smaller than that in lean mice. Our human studies show that serum levels of FGF21 in healthy men are strongly elevated (by 4.4-fold compared to the fed state) after overnight fasting but are reduced after refeeding. In summary, our results demonstrate that FGF21 is involved in regulating adaptation to fasting at the early stage in both rodents and humans. The consistent findings in humans and mice suggest that FGF21 might play similar metabolic roles in humans as those observed in animals, and support the notion that FGF21 can be a potential therapeutic target for treating metabolic disorders in humans.